ABSTRACT
A large number of workers are potentially exposed to cadmium during mining and processing. Therefore, there is a concern regarding the potential carcinogenic hazards of cadmium to exposed workers. Studies have been performed to determine if cadmium chloride (CdCl(2)) can induce morphological cell transformation, DNA from CdCl(2)-induced transformed cells can transform other mammalian cells, and the transformed cells induced by CdCl(2) can form tumors in nude mice. BALB/c-3T3 cells were treated with different concentrations of CdCl(2) for 72 h. The frequency of transformed foci from each treatment was determined after cells were cultured for 4 to 5 weeks. DNAs from five CdCl(2)-induced transformed cell lines were isolated and gene transfection assay was performed using NIH-3T3 cells. Non-transformed BALB/c-3T3 cells and cells from 10 transformed cell lines induced by CdCl(2) were injected into both axillary regions of nude mice. Mice were screened once a week for the appearance and size of tumors. CdCl(2) caused a statistically significant, concentration-related increase in the transformation frequency. DNA from all five CdCl(2)-induced transformed cell lines tested was found to induce varying degrees of transfection-mediated transformation in NIH-3T3 cells. All 10 CdCl(2)-induced transformed cell lines formed fibrosarcomas in nude mice within 39 days of inoculation. Within this time period, no tumors were found in nude mice injected with non-transformed BALB/c-3T3 cells. These results indicate that CdCl(2) is capable of inducing morphological cell transformation and that the transformed cells induced by CdCl(2) are potentially tumorigenic.
Subject(s)
Cadmium Chloride/toxicity , Carcinogens/toxicity , Cell Transformation, Neoplastic/drug effects , 3T3 Cells/drug effects , 3T3 Cells/pathology , Animals , Carcinogenicity Tests , Cell Line, Transformed , DNA, Neoplasm , Dose-Response Relationship, Drug , Female , Mice , Mice, Inbred BALB C , Mice, Nude , TransfectionABSTRACT
Our previous study showed that both 1-nitropyrene (1-NP) and dibenzo(a,i)pyrene (DBP) induced enhanced growth variants (EGVs) in primary cultures of rat tracheal epithelial (RTE) cells exposed in vivo. Cell lines were established from some of the EGVs. Further studies, using anchorage-independent growth in soft agar and tumorigenicity in athymic nude mice, were performed to determine the neoplastic potential of EGVs induced by 1-NP and DBP. Results show that three of five from DBP- and five of five from 1-NP-induced cell lines displayed anchorage-independent growth. The colony forming efficiency (CFE) from DBP-induced cell lines was 0.067 per thousand and CFE from 1-NP-induced cell lines was 0.151 per thousand. There is a significant difference between the two CFEs (mu = 12.08, P<0. 01). Two of five DBP- and five of five 1-NP-induced cell lines produced squamous cell carcinomas (SCC) in nude mice. The rate of tumorigenicity counted by injected sites was 20% (6/30) for DBP-induced cell lines and 57% (17/30) for 1-NP-induced cell lines. There is a significant difference between the results of tumorigenicity from the cell lines induced by the two different compounds (chi(2)=8.53, P<0.01). Neither of the two cell lines from spontaneously developed foci grew in soft agar or produced SCC in nude mice. It seems that the neoplastic potential of transformed RTE cells induced by 1-NP was higher than that of DBP.
Subject(s)
Benzopyrenes/toxicity , Carcinogens/toxicity , Cell Transformation, Neoplastic/drug effects , Pyrenes/toxicity , Animals , Carcinogenicity Tests , Carcinoma, Squamous Cell/chemically induced , Carcinoma, Squamous Cell/pathology , Cell Adhesion , Cell Division , Cell Line , Cell Transformation, Neoplastic/pathology , Female , Mice , Mice, Nude , Neoplasm Transplantation , Rats , Tracheal Neoplasms/chemically induced , Tracheal Neoplasms/pathology , Transplantation, HeterologousABSTRACT
The rat tracheal epithelial (RTE) cell transformation assay was performed to determine the transforming activity of diesel emission particles (DEPs) and two related compounds, 1-nitropyrene (1-NP) and dibenzo(a,i)pyrene (DBP). RTE cells were treated with these agents in vitro and in vivo. Transformed cells from foci induced by these agents were passaged over 20 times to establish immortal cell lines. Results show that (1) DEPs- and 1-NP-induced cell transformation only with the in vivo exposure (30-75 mg/kg bw DEPs and 15-60 mg/kg bw 1-NP); (2) positive dose-related responses to DBP were found with both in vitro (0.05-0.50 microg/ml) and in vivo (7.5-30 mg/kg bw) exposures; (3) the fraction of transformed foci becoming cell lines was in the order of 1-NP(25/48) > DBP(8/28) > DEPs(0/30). These results indicate that (1) DEPs, 1-NP and DBP are capable of transforming rat tracheal epithelial cells, however, the transforming activity of DEPs and -NP may be dependent on metabolic activation, and (2) transformed cells induced by DEPs have a very low probability, if any, of becoming cell lines.
